WNT3A_HUMAN
ID WNT3A_HUMAN Reviewed; 352 AA.
AC P56704; Q3SY79; Q3SY80; Q969P2;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2002, sequence version 2.
DT 03-AUG-2022, entry version 192.
DE RecName: Full=Protein Wnt-3a;
DE Flags: Precursor;
GN Name=WNT3A;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RX PubMed=11414706; DOI=10.1006/bbrc.2001.5105;
RA Saitoh T., Hirai M., Katoh M.;
RT "Molecular cloning and characterization of WNT3a and WNT14 clustered in
RT human chromosome 1q42 region.";
RL Biochem. Biophys. Res. Commun. 284:1168-1175(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 207-330.
RC TISSUE=Mammary gland;
RX PubMed=8168088;
RA Huguet E.L., McMahon J.A., McMahon A.P., Bicknell R., Harris A.L.;
RT "Differential expression of human Wnt genes 2, 3, 4, and 7B in human breast
RT cell lines and normal and disease states of human breast tissue.";
RL Cancer Res. 54:2615-2621(1994).
RN [6]
RP INTERACTION WITH GPC3.
RX PubMed=16227623; DOI=10.1074/jbc.m507004200;
RA Capurro M.I., Shi W., Sandal S., Filmus J.;
RT "Processing by convertases is not required for glypican-3-induced
RT stimulation of hepatocellular carcinoma growth.";
RL J. Biol. Chem. 280:41201-41206(2005).
RN [7]
RP INTERACTION WITH WLS.
RX PubMed=16678095; DOI=10.1016/j.cell.2006.02.049;
RA Baenziger C., Soldini D., Schuett C., Zipperlen P., Hausmann G., Basler K.;
RT "Wntless, a conserved membrane protein dedicated to the secretion of Wnt
RT proteins from signaling cells.";
RL Cell 125:509-522(2006).
RN [8]
RP INTERACTION WITH LRP6 IN THE WNT/FZD/LRP6 COMPLEX, AND FUNCTION.
RX PubMed=20093360; DOI=10.1074/jbc.m109.092130;
RA Bourhis E., Tam C., Franke Y., Bazan J.F., Ernst J., Hwang J., Costa M.,
RA Cochran A.G., Hannoush R.N.;
RT "Reconstitution of a frizzled8.Wnt3a.LRP6 signaling complex reveals
RT multiple Wnt and Dkk1 binding sites on LRP6.";
RL J. Biol. Chem. 285:9172-9179(2010).
RN [9]
RP PALMITOLEOYLATION AT SER-209 BY PORCN, AND MUTAGENESIS OF SER-209.
RX PubMed=20826466; DOI=10.1242/jcs.072132;
RA Coombs G.S., Yu J., Canning C.A., Veltri C.A., Covey T.M., Cheong J.K.,
RA Utomo V., Banerjee N., Zhang Z.H., Jadulco R.C., Concepcion G.P.,
RA Bugni T.S., Harper M.K., Mihalek I., Jones C.M., Ireland C.M.,
RA Virshup D.M.;
RT "WLS-dependent secretion of WNT3A requires Ser209 acylation and vacuolar
RT acidification.";
RL J. Cell Sci. 123:3357-3367(2010).
RN [10]
RP INTERACTION WITH APCDD1.
RX PubMed=20393562; DOI=10.1038/nature08875;
RA Shimomura Y., Agalliu D., Vonica A., Luria V., Wajid M., Baumer A.,
RA Belli S., Petukhova L., Schinzel A., Brivanlou A.H., Barres B.A.,
RA Christiano A.M.;
RT "APCDD1 is a novel Wnt inhibitor mutated in hereditary hypotrichosis
RT simplex.";
RL Nature 464:1043-1047(2010).
RN [11]
RP FUNCTION, PRELIMINARY CYSTEINE PALMITOYLATION, PALMITOLEOYLATION AT
RP SER-209, GLYCOSYLATION AT ASN-87 AND ASN-298, AND MUTAGENESIS OF ASN-87;
RP SER-209 AND ASN-298.
RX PubMed=21244856; DOI=10.1016/j.cellsig.2011.01.007;
RA Doubravska L., Krausova M., Gradl D., Vojtechova M., Tumova L., Lukas J.,
RA Valenta T., Pospichalova V., Fafilek B., Plachy J., Sebesta O., Korinek V.;
RT "Fatty acid modification of Wnt1 and Wnt3a at serine is prerequisite for
RT lipidation at cysteine and is essential for Wnt signalling.";
RL Cell. Signal. 23:837-848(2011).
RN [12]
RP FUNCTION, SUBCELLULAR LOCATION, DISULFIDE BONDS, AND MUTAGENESIS OF
RP SER-209; CYS-334 AND CYS-335.
RX PubMed=24841207; DOI=10.1074/jbc.m114.575027;
RA MacDonald B.T., Hien A., Zhang X., Iranloye O., Virshup D.M.,
RA Waterman M.L., He X.;
RT "Disulfide bond requirements for active wnt ligands.";
RL J. Biol. Chem. 289:18122-18136(2014).
RN [13]
RP LACK OF PALMITOYLATION AT CYS-77, AND PALMITOLEOYLATION AT SER-209 BY
RP PORCN.
RX PubMed=24292069; DOI=10.1038/nchembio.1392;
RA Gao X., Hannoush R.N.;
RT "Single-cell imaging of Wnt palmitoylation by the acyltransferase
RT porcupine.";
RL Nat. Chem. Biol. 10:61-68(2014).
RN [14]
RP PALMITOLEOYLATION AT SER-209, AND DEPALMITOLEOYLATION.
RX PubMed=25731175; DOI=10.1038/nature14259;
RA Kakugawa S., Langton P.F., Zebisch M., Howell S.A., Chang T.H., Liu Y.,
RA Feizi T., Bineva G., O'Reilly N., Snijders A.P., Jones E.Y., Vincent J.P.;
RT "Notum deacylates Wnt proteins to suppress signalling activity.";
RL Nature 519:187-192(2015).
RN [15]
RP INTERACTION WITH AFM, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=26902720; DOI=10.7554/elife.11621;
RA Mihara E., Hirai H., Yamamoto H., Tamura-Kawakami K., Matano M.,
RA Kikuchi A., Sato T., Takagi J.;
RT "Active and water-soluble form of lipidated Wnt protein is maintained by a
RT serum glycoprotein afamin/alpha-albumin.";
RL Elife 5:0-0(2016).
RN [16]
RP INTERACTION WITH PKD1.
RX PubMed=27214281; DOI=10.1038/ncb3363;
RA Kim S., Nie H., Nesin V., Tran U., Outeda P., Bai C.X., Keeling J.,
RA Maskey D., Watnick T., Wessely O., Tsiokas L.;
RT "The polycystin complex mediates Wnt/Ca(2+) signalling.";
RL Nat. Cell Biol. 18:752-764(2016).
CC -!- FUNCTION: Ligand for members of the frizzled family of seven
CC transmembrane receptors (Probable). Functions in the canonical Wnt
CC signaling pathway that results in activation of transcription factors
CC of the TCF/LEF family (PubMed:20093360, PubMed:21244856,
CC PubMed:24841207, PubMed:26902720). Required for normal embryonic
CC mesoderm development and formation of caudal somites. Required for
CC normal morphogenesis of the developing neural tube (By similarity).
CC Mediates self-renewal of the stem cells at the bottom on intestinal
CC crypts (in vitro) (PubMed:26902720). {ECO:0000250|UniProtKB:P27467,
CC ECO:0000269|PubMed:20093360, ECO:0000269|PubMed:21244856,
CC ECO:0000269|PubMed:24841207, ECO:0000269|PubMed:26902720, ECO:0000305}.
CC -!- SUBUNIT: Forms a soluble 1:1 complex with AFM; this prevents
CC oligomerization and is required for prolonged biological activity
CC (PubMed:26902720). The complex with AFM may represent the physiological
CC form in body fluids (PubMed:26902720). Homooligomer; disulfide-linked,
CC leading to inactivation (By similarity). Interacts with PORCN
CC (PubMed:20826466). Interacts with APCDD1 and WLS (PubMed:16678095,
CC PubMed:20393562). Component of the Wnt-Fzd-LRP5-LRP6 signaling complex
CC that contains a WNT protein, a FZD protein and LRP5 or LRP6. Interacts
CC directly in the complex with LRP6 (PubMed:20093360). Interacts with
CC glypican GPC3 (PubMed:16227623). Interacts with PKD1 (via extracellular
CC domain) (PubMed:27214281). {ECO:0000250|UniProtKB:P27467,
CC ECO:0000269|PubMed:16227623, ECO:0000269|PubMed:16678095,
CC ECO:0000269|PubMed:20093360, ECO:0000269|PubMed:20393562,
CC ECO:0000269|PubMed:24841207, ECO:0000269|PubMed:26902720,
CC ECO:0000269|PubMed:27214281, ECO:0000305|PubMed:20826466}.
CC -!- INTERACTION:
CC P56704; Q8J025: APCDD1; NbExp=3; IntAct=EBI-6173037, EBI-2683489;
CC P56704; Q9H461: FZD8; NbExp=2; IntAct=EBI-6173037, EBI-6254212;
CC P56704; O75581: LRP6; NbExp=2; IntAct=EBI-6173037, EBI-910915;
CC P56704; Q5T9L3: WLS; NbExp=4; IntAct=EBI-6173037, EBI-2868748;
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix {ECO:0000250|UniProtKB:P27467}. Secreted
CC {ECO:0000269|PubMed:24841207, ECO:0000269|PubMed:26902720}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P56704-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P56704-2; Sequence=VSP_046558;
CC -!- TISSUE SPECIFICITY: Moderately expressed in placenta and at low levels
CC in adult lung, spleen, and prostate. {ECO:0000269|PubMed:11414706}.
CC -!- PTM: Palmitoleoylation by PORCN is required for efficient binding to
CC frizzled receptors. Palmitoleoylation is required for proper
CC trafficking to cell surface, vacuolar acidification is critical to
CC release palmitoleoylated WNT3A from WLS in secretory vesicles
CC (PubMed:20826466, PubMed:21244856, PubMed:24292069). Depalmitoleoylated
CC by NOTUM, leading to inhibit Wnt signaling pathway, possibly by
CC promoting disulfide bond formation and oligomerization
CC (PubMed:25731175). {ECO:0000269|PubMed:20826466,
CC ECO:0000269|PubMed:21244856, ECO:0000269|PubMed:24292069,
CC ECO:0000269|PubMed:25731175}.
CC -!- PTM: Proteolytic processing by TIKI1 and TIKI2 promotes oxidation and
CC formation of large disulfide-bond oligomers, leading to inactivation of
CC WNT3A. {ECO:0000250|UniProtKB:P27467}.
CC -!- PTM: Disulfide bonds have critical and distinct roles in secretion and
CC activity. Loss of each conserved cysteine in WNT3A results in high
CC molecular weight oxidized Wnt oligomers, which are formed through
CC inter-Wnt disulfide bonding. {ECO:0000269|PubMed:24841207}.
CC -!- SIMILARITY: Belongs to the Wnt family. {ECO:0000305}.
CC -!- CAUTION: A palmitoylation site was proposed at Cys-77, but it was later
CC shown that this cysteine is engaged in a disulfide bond
CC (PubMed:24292069). {ECO:0000269|PubMed:24292069}.
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DR EMBL; AB060284; BAB61052.1; -; mRNA.
DR EMBL; AK056278; BAB71136.1; -; mRNA.
DR EMBL; AL136379; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC103921; AAI03922.1; -; mRNA.
DR EMBL; BC103922; AAI03923.1; -; mRNA.
DR EMBL; BC103923; AAI03924.1; -; mRNA.
DR CCDS; CCDS1564.1; -. [P56704-1]
DR RefSeq; NP_149122.1; NM_033131.3. [P56704-1]
DR PDB; 7DRT; EM; 2.20 A; A=1-352.
DR PDBsum; 7DRT; -.
DR AlphaFoldDB; P56704; -.
DR SMR; P56704; -.
DR BioGRID; 124599; 40.
DR DIP; DIP-58592N; -.
DR IntAct; P56704; 20.
DR STRING; 9606.ENSP00000284523; -.
DR BindingDB; P56704; -.
DR ChEMBL; CHEMBL1255137; -.
DR GlyGen; P56704; 2 sites.
DR iPTMnet; P56704; -.
DR PhosphoSitePlus; P56704; -.
DR BioMuta; WNT3A; -.
DR DMDM; 20532424; -.
DR MassIVE; P56704; -.
DR PaxDb; P56704; -.
DR PeptideAtlas; P56704; -.
DR PRIDE; P56704; -.
DR ProteomicsDB; 56937; -. [P56704-1]
DR Antibodypedia; 34658; 607 antibodies from 36 providers.
DR DNASU; 89780; -.
DR Ensembl; ENST00000284523.2; ENSP00000284523.1; ENSG00000154342.6. [P56704-1]
DR GeneID; 89780; -.
DR KEGG; hsa:89780; -.
DR MANE-Select; ENST00000284523.2; ENSP00000284523.1; NM_033131.4; NP_149122.1.
DR UCSC; uc001hrq.3; human. [P56704-1]
DR CTD; 89780; -.
DR DisGeNET; 89780; -.
DR GeneCards; WNT3A; -.
DR HGNC; HGNC:15983; WNT3A.
DR HPA; ENSG00000154342; Tissue enriched (placenta).
DR MalaCards; WNT3A; -.
DR MIM; 606359; gene.
DR neXtProt; NX_P56704; -.
DR OpenTargets; ENSG00000154342; -.
DR Orphanet; 85193; Idiopathic juvenile osteoporosis.
DR PharmGKB; PA38074; -.
DR VEuPathDB; HostDB:ENSG00000154342; -.
DR eggNOG; KOG3913; Eukaryota.
DR GeneTree; ENSGT00940000160510; -.
DR HOGENOM; CLU_033039_1_0_1; -.
DR InParanoid; P56704; -.
DR OMA; GLTHVMA; -.
DR OrthoDB; 965867at2759; -.
DR PhylomeDB; P56704; -.
DR TreeFam; TF105310; -.
DR PathwayCommons; P56704; -.
DR Reactome; R-HSA-201681; TCF dependent signaling in response to WNT.
DR Reactome; R-HSA-3238698; WNT ligand biogenesis and trafficking.
DR Reactome; R-HSA-373080; Class B/2 (Secretin family receptors).
DR Reactome; R-HSA-3772470; Negative regulation of TCF-dependent signaling by WNT ligand antagonists.
DR Reactome; R-HSA-4641262; Disassembly of the destruction complex and recruitment of AXIN to the membrane.
DR Reactome; R-HSA-4641263; Regulation of FZD by ubiquitination.
DR Reactome; R-HSA-5340588; Signaling by RNF43 mutants.
DR SignaLink; P56704; -.
DR SIGNOR; P56704; -.
DR BioGRID-ORCS; 89780; 14 hits in 1072 CRISPR screens.
DR ChiTaRS; WNT3A; human.
DR GeneWiki; WNT3A; -.
DR GenomeRNAi; 89780; -.
DR Pharos; P56704; Tchem.
DR PRO; PR:P56704; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P56704; protein.
DR Bgee; ENSG00000154342; Expressed in placenta and 24 other tissues.
DR GO; GO:0009986; C:cell surface; ISS:BHF-UCL.
DR GO; GO:0031901; C:early endosome membrane; TAS:Reactome.
DR GO; GO:0030666; C:endocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; TAS:Reactome.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0005796; C:Golgi lumen; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0098793; C:presynapse; IEA:GOC.
DR GO; GO:1990851; C:Wnt-Frizzled-LRP5/6 complex; IDA:ParkinsonsUK-UCL.
DR GO; GO:0039706; F:co-receptor binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0005125; F:cytokine activity; IBA:GO_Central.
DR GO; GO:0005109; F:frizzled binding; IBA:GO_Central.
DR GO; GO:0019904; F:protein domain specific binding; IEA:Ensembl.
DR GO; GO:0048018; F:receptor ligand activity; IDA:BHF-UCL.
DR GO; GO:0005102; F:signaling receptor binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0003713; F:transcription coactivator activity; IEA:Ensembl.
DR GO; GO:0090245; P:axis elongation involved in somitogenesis; IEA:Ensembl.
DR GO; GO:0007411; P:axon guidance; IEA:Ensembl.
DR GO; GO:0042100; P:B cell proliferation; IEA:Ensembl.
DR GO; GO:0090676; P:calcium ion transmembrane transport via low voltage-gated calcium channel; IEA:Ensembl.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; IDA:UniProtKB.
DR GO; GO:0061317; P:canonical Wnt signaling pathway involved in cardiac muscle cell fate commitment; IDA:BHF-UCL.
DR GO; GO:0045165; P:cell fate commitment; IBA:GO_Central.
DR GO; GO:0008283; P:cell population proliferation; IMP:UniProtKB.
DR GO; GO:0021846; P:cell proliferation in forebrain; ISS:BHF-UCL.
DR GO; GO:0033278; P:cell proliferation in midbrain; TAS:ParkinsonsUK-UCL.
DR GO; GO:0071300; P:cellular response to retinoic acid; ISS:UniProtKB.
DR GO; GO:0010387; P:COP9 signalosome assembly; ISS:BHF-UCL.
DR GO; GO:0021904; P:dorsal/ventral neural tube patterning; IEA:Ensembl.
DR GO; GO:0030198; P:extracellular matrix organization; IEA:Ensembl.
DR GO; GO:0045444; P:fat cell differentiation; IEA:Ensembl.
DR GO; GO:0001947; P:heart looping; IEA:Ensembl.
DR GO; GO:0030097; P:hemopoiesis; IEA:Ensembl.
DR GO; GO:0021766; P:hippocampus development; IEA:Ensembl.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0042472; P:inner ear morphogenesis; IEA:Ensembl.
DR GO; GO:0030879; P:mammary gland development; IEA:Ensembl.
DR GO; GO:0050804; P:modulation of chemical synaptic transmission; IEA:Ensembl.
DR GO; GO:0045445; P:myoblast differentiation; IEA:Ensembl.
DR GO; GO:0048843; P:negative regulation of axon extension involved in axon guidance; IEA:Ensembl.
DR GO; GO:1904339; P:negative regulation of dopaminergic neuron differentiation; IEA:Ensembl.
DR GO; GO:0045599; P:negative regulation of fat cell differentiation; IEA:Ensembl.
DR GO; GO:0003136; P:negative regulation of heart induction by canonical Wnt signaling pathway; IDA:BHF-UCL.
DR GO; GO:0050768; P:negative regulation of neurogenesis; ISS:BHF-UCL.
DR GO; GO:1901215; P:negative regulation of neuron death; IEA:Ensembl.
DR GO; GO:0010977; P:negative regulation of neuron projection development; ISS:UniProtKB.
DR GO; GO:0030182; P:neuron differentiation; ISS:UniProtKB.
DR GO; GO:0001649; P:osteoblast differentiation; IEA:Ensembl.
DR GO; GO:0048343; P:paraxial mesodermal cell fate commitment; IEA:Ensembl.
DR GO; GO:0070527; P:platelet aggregation; IEA:Ensembl.
DR GO; GO:0030890; P:positive regulation of B cell proliferation; IEA:Ensembl.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IDA:BHF-UCL.
DR GO; GO:2000081; P:positive regulation of canonical Wnt signaling pathway involved in controlling type B pancreatic cell proliferation; IEA:Ensembl.
DR GO; GO:2000727; P:positive regulation of cardiac muscle cell differentiation; IDA:BHF-UCL.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISS:BHF-UCL.
DR GO; GO:2000049; P:positive regulation of cell-cell adhesion mediated by cadherin; IEA:Ensembl.
DR GO; GO:0048697; P:positive regulation of collateral sprouting in absence of injury; IEA:Ensembl.
DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; IEA:Ensembl.
DR GO; GO:0001819; P:positive regulation of cytokine production; IEA:Ensembl.
DR GO; GO:0061184; P:positive regulation of dermatome development; IDA:BHF-UCL.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IEA:Ensembl.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:BHF-UCL.
DR GO; GO:2000347; P:positive regulation of hepatocyte proliferation; IEA:Ensembl.
DR GO; GO:0048337; P:positive regulation of mesodermal cell fate specification; IDA:BHF-UCL.
DR GO; GO:2000179; P:positive regulation of neural precursor cell proliferation; IEA:Ensembl.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IDA:BHF-UCL.
DR GO; GO:0032092; P:positive regulation of protein binding; IDA:BHF-UCL.
DR GO; GO:1903078; P:positive regulation of protein localization to plasma membrane; IEA:Ensembl.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:BHF-UCL.
DR GO; GO:0061098; P:positive regulation of protein tyrosine kinase activity; IEA:Ensembl.
DR GO; GO:0002092; P:positive regulation of receptor internalization; IDA:BHF-UCL.
DR GO; GO:0048643; P:positive regulation of skeletal muscle tissue development; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:BHF-UCL.
DR GO; GO:0036342; P:post-anal tail morphogenesis; IEA:Ensembl.
DR GO; GO:0099527; P:postsynapse to nucleus signaling pathway; IEA:Ensembl.
DR GO; GO:0099054; P:presynapse assembly; TAS:ParkinsonsUK-UCL.
DR GO; GO:0008104; P:protein localization; IEA:Ensembl.
DR GO; GO:0070507; P:regulation of microtubule cytoskeleton organization; IEA:Ensembl.
DR GO; GO:1905606; P:regulation of presynapse assembly; IDA:SynGO.
DR GO; GO:0050807; P:regulation of synapse organization; IDA:SynGO.
DR GO; GO:0062009; P:secondary palate development; IMP:BHF-UCL.
DR GO; GO:0035914; P:skeletal muscle cell differentiation; IEA:Ensembl.
DR GO; GO:0048103; P:somatic stem cell division; IEA:Ensembl.
DR GO; GO:0021527; P:spinal cord association neuron differentiation; IEA:Ensembl.
DR GO; GO:0036465; P:synaptic vesicle recycling; TAS:ParkinsonsUK-UCL.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0021874; P:Wnt signaling pathway involved in forebrain neuroblast division; IEA:Ensembl.
DR GO; GO:1904953; P:Wnt signaling pathway involved in midbrain dopaminergic neuron differentiation; TAS:ParkinsonsUK-UCL.
DR Gene3D; 3.30.2460.20; -; 1.
DR InterPro; IPR005817; Wnt.
DR InterPro; IPR009141; Wnt3.
DR InterPro; IPR043158; Wnt_C.
DR InterPro; IPR018161; Wnt_CS.
DR PANTHER; PTHR12027; PTHR12027; 1.
DR Pfam; PF00110; wnt; 1.
DR PRINTS; PR01843; WNT3PROTEIN.
DR PRINTS; PR01349; WNTPROTEIN.
DR SMART; SM00097; WNT1; 1.
DR PROSITE; PS00246; WNT1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Developmental protein; Disulfide bond;
KW Extracellular matrix; Glycoprotein; Lipoprotein; Reference proteome;
KW Secreted; Signal; Wnt signaling pathway.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..352
FT /note="Protein Wnt-3a"
FT /id="PRO_0000041418"
FT SITE 26..27
FT /note="Cleavage; by TIKI1 and TIKI2"
FT /evidence="ECO:0000250|UniProtKB:P27467"
FT LIPID 209
FT /note="O-palmitoleoyl serine; by PORCN"
FT /evidence="ECO:0000269|PubMed:20826466,
FT ECO:0000269|PubMed:21244856, ECO:0000269|PubMed:24292069,
FT ECO:0000269|PubMed:25731175"
FT CARBOHYD 87
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:21244856"
FT CARBOHYD 298
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:21244856"
FT DISULFID 77..88
FT /evidence="ECO:0000269|PubMed:24292069"
FT DISULFID 128..136
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 138..155
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 203..217
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 205..212
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 281..312
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 297..307
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 311..351
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 327..342
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 329..339
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 334..335
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT VAR_SEQ 352
FT /note="K -> KNPGSRAGNSAHQPPHPQPPVRFHPPLRRAGKVP (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_046558"
FT MUTAGEN 87
FT /note="N->Q: Strongly reduced ability to stimulate Wnt-
FT responsive reporters; when associated with Q-298."
FT /evidence="ECO:0000269|PubMed:21244856"
FT MUTAGEN 209
FT /note="S->A: Abrogates WLS binding."
FT /evidence="ECO:0000269|PubMed:20826466,
FT ECO:0000269|PubMed:21244856, ECO:0000269|PubMed:24841207"
FT MUTAGEN 209
FT /note="S->A: Complete loss of palmitoleoylation."
FT /evidence="ECO:0000269|PubMed:20826466,
FT ECO:0000269|PubMed:21244856, ECO:0000269|PubMed:24841207"
FT MUTAGEN 209
FT /note="S->T: No effect on palmitoleoylation and secretion;
FT the threonine can functionally replace the serine."
FT /evidence="ECO:0000269|PubMed:20826466,
FT ECO:0000269|PubMed:21244856, ECO:0000269|PubMed:24841207"
FT MUTAGEN 298
FT /note="N->Q: Strongly reduced ability to stimulate Wnt-
FT responsive reporters; when associated with Q-87."
FT /evidence="ECO:0000269|PubMed:21244856"
FT MUTAGEN 334
FT /note="C->A: No signaling activity despite the presence of
FT significant amounts of secreted monomeric Wnt3a, exhibits
FT dominant negative properties; when associated with A-335."
FT /evidence="ECO:0000269|PubMed:24841207"
FT MUTAGEN 335
FT /note="C->A: No signaling activity despite the presence of
FT significant amounts of secreted monomeric Wnt3a, exhibits
FT dominant negative properties; when associated with A-334."
FT /evidence="ECO:0000269|PubMed:24841207"
FT HELIX 23..27
FT /evidence="ECO:0007829|PDB:7DRT"
FT HELIX 29..31
FT /evidence="ECO:0007829|PDB:7DRT"
FT STRAND 35..38
FT /evidence="ECO:0007829|PDB:7DRT"
FT STRAND 42..44
FT /evidence="ECO:0007829|PDB:7DRT"
FT HELIX 50..58
FT /evidence="ECO:0007829|PDB:7DRT"
FT HELIX 63..80
FT /evidence="ECO:0007829|PDB:7DRT"
FT TURN 81..83
FT /evidence="ECO:0007829|PDB:7DRT"
FT STRAND 94..96
FT /evidence="ECO:0007829|PDB:7DRT"
FT HELIX 100..103
FT /evidence="ECO:0007829|PDB:7DRT"
FT HELIX 107..129
FT /evidence="ECO:0007829|PDB:7DRT"
FT STRAND 134..137
FT /evidence="ECO:0007829|PDB:7DRT"
FT STRAND 145..148
FT /evidence="ECO:0007829|PDB:7DRT"
FT TURN 150..153
FT /evidence="ECO:0007829|PDB:7DRT"
FT HELIX 161..169
FT /evidence="ECO:0007829|PDB:7DRT"
FT HELIX 170..172
FT /evidence="ECO:0007829|PDB:7DRT"
FT STRAND 176..178
FT /evidence="ECO:0007829|PDB:7DRT"
FT HELIX 179..197
FT /evidence="ECO:0007829|PDB:7DRT"
FT STRAND 200..207
FT /evidence="ECO:0007829|PDB:7DRT"
FT STRAND 210..220
FT /evidence="ECO:0007829|PDB:7DRT"
FT HELIX 224..237
FT /evidence="ECO:0007829|PDB:7DRT"
FT STRAND 239..246
FT /evidence="ECO:0007829|PDB:7DRT"
FT STRAND 248..251
FT /evidence="ECO:0007829|PDB:7DRT"
FT STRAND 253..258
FT /evidence="ECO:0007829|PDB:7DRT"
FT TURN 260..262
FT /evidence="ECO:0007829|PDB:7DRT"
FT STRAND 267..269
FT /evidence="ECO:0007829|PDB:7DRT"
FT TURN 285..288
FT /evidence="ECO:0007829|PDB:7DRT"
FT STRAND 300..304
FT /evidence="ECO:0007829|PDB:7DRT"
FT HELIX 307..310
FT /evidence="ECO:0007829|PDB:7DRT"
FT STRAND 312..314
FT /evidence="ECO:0007829|PDB:7DRT"
FT STRAND 319..328
FT /evidence="ECO:0007829|PDB:7DRT"
FT STRAND 333..335
FT /evidence="ECO:0007829|PDB:7DRT"
FT STRAND 340..348
FT /evidence="ECO:0007829|PDB:7DRT"
SQ SEQUENCE 352 AA; 39365 MW; A317BD6D4A73920B CRC64;
MAPLGYFLLL CSLKQALGSY PIWWSLAVGP QYSSLGSQPI LCASIPGLVP KQLRFCRNYV
EIMPSVAEGI KIGIQECQHQ FRGRRWNCTT VHDSLAIFGP VLDKATRESA FVHAIASAGV
AFAVTRSCAE GTAAICGCSS RHQGSPGKGW KWGGCSEDIE FGGMVSREFA DARENRPDAR
SAMNRHNNEA GRQAIASHMH LKCKCHGLSG SCEVKTCWWS QPDFRAIGDF LKDKYDSASE
MVVEKHRESR GWVETLRPRY TYFKVPTERD LVYYEASPNF CEPNPETGSF GTRDRTCNVS
SHGIDGCDLL CCGRGHNARA ERRREKCRCV FHWCCYVSCQ ECTRVYDVHT CK
